New method may accelerate drug discovery for difficult diseases like P...( CAMBRIDGE Mass. (July 13 2009) Whit...)

CAMBRIDGE, Mass. (July 13, 2009) Whitehead Institute scientists have developed a rapid, inexpensive drug-screening method that could be used to target diseases that until now have stymied drug developers, such as Parkinson's disease. This technique uses baker's yeast to synthesize and screen the molecules, cutting target discovery and preliminary testing time to a matter of weeks.

The current drug discovery process is arduous, requiring identification of potential drug targets, synthesis of large collections of molecular compounds that might interact effectively with an identified target, screening of compounds with expensive assays and robotics, and defining the compounds' structures largely through trial and error. At the end of this months-long process, a large team of chemists and biologists usually deem only 1% or fewer of the compounds worthy of further testing in living cells.

A novel method, demonstrated by Whitehead scientists and described in the July 13 issue of Nature Chemical Biology, uses baker's yeast cells to perform most of the same work in a matter of weeks, with the added benefit that the testing is all done in living cells. At the core of this approach are extremely small proteins, called cyclic peptides, which are capable of targeting the protein-protein interactions found in almost every cellular process. Most current drugs act by wedging themselves into small pockets on the surfaces of target proteins. However, these traditional drugs are unable to adhere to smooth, flat protein surfaces, rendering the drugs ineffective for inhibiting the key interactions among proteins that occur at these surfaces. Cyclic peptides have the ability to bind where traditional drugs cannot, allowing for the identification of previously overlooked targets to fight disease.

"We're getting at a chemical space that is very underexplored by traditional drug development and screening," says Joshua Kritzer, author of the N
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